Current Activities Research Articles

Protein kinase C epsilon-mediated modulation of T-type calcium channels underlies alcohol withdrawal hyperexcitability in the midline thalamus.

Millions of people struggle with alcohol use disorder (AUD). Abrupt abstinence after a period of chronic alcohol use can precipitate the alcohol withdrawal syndrome (AWS), which includes hyperexcitability and, potentially, seizures. We have shown that T-type Ca2+ channels are novel, sensitive targets of alcohol, an effect that is dependent upon protein kinase C (PKC). The purpose of this study was to (1) understand midline thalamic neuronal hyperexcitability during alcohol withdrawal and its dependence on PKC; (2) characterize T channel functional changes using both current clamp and voltage clamp methods; and (3) determine which PKC isoform may be responsible for alcohol withdrawal (WD) effects. Whole-cell patch clamp recordings were performed in midline thalamic neurons in brain slices prepared from C57bl/6 mice that underwent chronic intermittent alcohol exposure in a standard vapor chamber model. The recordings were compared to those from air-exposed controls. T-channel inactivation curves and burst responses were acquired through voltage-clamp and current-clamp recordings, respectively. Whole-cell voltage clamp recordings of native T-type current exhibited a depolarizing shift in the voltage-dependency of inactivation during alcohol withdrawal compared to air-exposed controls. A PKCε translocation inhibitor peptide mitigated this change. Current clamp recordings demonstrated more spikes per burst during alcohol withdrawal. Consistent with voltage clamp findings, the PKCɛ translocation inhibitor peptide reduced the number of spikes per burst after WD. We found that alcohol WD produces T channel-mediated hyperexcitability in the midline thalamus, produced in part by a shift in the inactivation curve consistent with greater availability of T current. WD effects on T current inactivation were reduced to control levels by blocking PKCε translocation. Our results demonstrate that PKCε translocation plays an important role in the regulation of alcohol withdrawal-induced hyperexcitability in midline thalamic circuitry.

3-Methyl-phenanthrene (3-MP) disrupts the electrical and contractile activity of the heart of the polar fish, navaga cod (Eleginus nawaga)

Alkylated polycyclic aromatic hydrocarbons are abundant in crude oil and are enriched during petroleum refinement but knowledge of their cardiotoxicity remains limited. Polycyclic aromatic hydrocarbons (PAHs) are considered the main hazardous components in crude oil and the tricyclic PAH phenanthrene has been singled out for its direct effects on cardiac tissue in mammals and fish. Here we test the impact of the monomethylated phenanthrene, 3-methylphenanthrene (3-MP), on the contractile and electrical function of the atrium and ventricle of a polar fish, the navaga cod (Eleginus nawaga). Using patch-clamp electrophysiology in atrial and ventricular cardiomyocytes we show that 3-MP is a potent inhibitor of the delayed rectifier current IKr (IC50 = 0.25 μM) and prolongs ventricular action potential duration. Unlike the parent compound phenanthrene, 3-MP did not reduce the amplitude of the L-type Ca2+ current (ICa) but it accelerated current inactivation thus reducing charge transfer across the myocyte membrane and compromising pressure development of the whole heart. 3-MP was a potent inhibitor (IC50 = 4.7 μM) of the sodium current (INa), slowing the upstroke of the action potential in isolated cells, slowing conduction velocity across the atrium measured with optical mapping, and increasing atrio-ventricular delay in a working whole heart preparation. Together, these findings reveal the strong cardiotoxic potential of this phenanthrene derivative on the fish heart. As 3-MP and other alkylated phenanthrenes comprise a large fraction of the PAHs in crude oil mixtures, these findings are worrisome for Arctic species facing increasing incidence of spills and leaks from the petroleum industry. 3-MP is also a major component of polluted air but is not routinely measured. This is also of concern if the hearts of humans and other terrestrial animals respond to this PAH in a similar manner to fish.

Sources, persistence, and current inactivation methods of foodborne pathogens in legumes

Legumes and legume-derived products are consumed in large quantities for their nutritional value as well as for their taste. Their sustainability and affordability are commendable, and legumes are a low-glycemic-index food that is high in protein and fibre while still being satiating. Legumes are commonly consumed as choice meals, particularly by vegetarians and vegans as a meat substitute, and they account for a significant portion of the dietary intake in many countries. The huge trend of vegan diets has prompted the industrial growth of legumes and pulses. The increased production within the shortest period to fulfil the expanding demand has put them at a higher risk of contamination with pathogenic microbes, rendering consumer safety uncertain. The objective of this review was to draw attention to the sources of microbiological contamination in legumes, the persistence of foodborne pathogens in legumes, and the existing techniques of foodborne pathogen inactivation. Water, surfaces, and human contact are all factors to consider, as is the risk linked with inadequate sanitation, poor equipment design, and improper handling. The foodborne pathogen, though seemingly unavoidable, can be minimized or inactivated using a variety of thermal and nonthermal procedures used prior to and after harvesting of legumes, as well as throughout the manufacturing and processing process.

Holistic-Guided Disentangled Learning With Cross-Video Semantics Mining for Concurrent First-Person and Third-Person Activity Recognition.

The popularity of wearable devices has increased the demands for the research on first-person activity recognition. However, most of the current first-person activity datasets are built based on the assumption that only the human-object interaction (HOI) activities, performed by the camera-wearer, are captured in the field of view. Since humans live in complicated scenarios, in addition to the first-person activities, it is likely that third-person activities performed by other people also appear. Analyzing and recognizing these two types of activities simultaneously occurring in a scene is important for the camera-wearer to understand the surrounding environments. To facilitate the research on concurrent first- and third-person activity recognition (CFT-AR), we first created a new activity dataset, namely PolyU concurrent first- and third-person (CFT) Daily, which exhibits distinct properties and challenges, compared with previous activity datasets. Since temporal asynchronism and appearance gap usually exist between the first- and third-person activities, it is crucial to learn robust representations from all the activity-related spatio-temporal positions. Thus, we explore both holistic scene-level and local instance-level (person-level) features to provide comprehensive and discriminative patterns for recognizing both first- and third-person activities. On the one hand, the holistic scene-level features are extracted by a 3-D convolutional neural network, which is trained to mine shared and sample-unique semantics between video pairs, via two well-designed attention-based modules and a self-knowledge distillation (SKD) strategy. On the other hand, we further leverage the extracted holistic features to guide the learning of instance-level features in a disentangled fashion, which aims to discover both spatially conspicuous patterns and temporally varied, yet critical, cues. Experimental results on the PolyU CFT Daily dataset validate that our method achieves the state-of-the-art performance.

Psychiatrists’ Engagement in Research as a Pathway towards the Expansion of Distributed Medical Education (DME): A Regional Analysis across Two Provinces in Atlantic Canada

In the context of Canadian medical education, Distributed Medical Education (DME) plays a crucial role in addressing healthcare disparities, particularly in rural areas. This study focuses on the Department of Psychiatry at Dalhousie University, analyzing psychiatrists’ engagement and willingness to participate in research at DME sites in Nova Scotia (NS) and New Brunswick (NB). The cross-sectional study, encompassing data from an environmental scan, surveyed 60 psychiatrists involved in medical education across seven health zones. Results revealed significant associations between gender, type of graduates, and specialist training. A majority of psychiatrists (68.3%) do not currently engage in mental health or translational research, citing barriers such as a lack of protected time and financial incentives. Notably, participants expressed interest in future research areas, including health services/quality improvement and addiction research. Geriatric psychiatry, predominantly female-dominated, lacked current research activities. The study emphasizes the need to address barriers and promote motivators, both intrinsic and extrinsic, to enhance psychiatrists’ research engagement. This strategic approach is essential for fostering active participation in research, thereby contributing to the expansion of DME sites in Atlantic Canada and beyond.

Lettering as an Artistic Activity to Integrate English Creative Learning with Hands-On Activity

The English language is challenging. Learning material is in its current state, and sometimes does not promote creativity. Students are looking for fun ways to learn the language. Lettering is one of current art activities that provides both creativity and fun. Applying lettering to the English language requires a module, to make it work. Keyword: English creative learning

Physical activity participation of university students in the United Kingdom

Every year more than 2.38 million students attend university in the United Kingdom. However, there is limited research up to this date addressing current physical activity participation of the university students in the United Kingdom. This study explored the current physical activity habits among students studying at university level in the United Kingdom. An online survey was administered and completed by 466 students from over 52 faculties. Participants answered questions on demographic variables such as gender, age, socioeconomic status of family, location of studies, types of studies, year of studies, living arrangements and monthly expenditure. They were provided the English version of the IPAQ-Short form and asked to fill out the questionnaire with their physical activity habits during a typical week of university study. Results identified 64.4% of the sample were “moderate” active, with 14.2% “high” and 18.5% “low” active as categorized by the IPAQ-Short form scoring. Disparities in physical activity participation were present on demographic variables such as gender, year of study and family socioeconomic level upon analysis by ANOVA. To conclude, a discussion of the results within the overall field of physical activity participation in higher education was positioned and critiqued.

A newborn active galactic nucleus in a star-forming galaxy

We report on the finding of a newborn active galactic nucleus (AGN), based on the observation of current AGN activity in a galaxy previously classified as non-active. We subsequently characterize the AGN's evolution. Black hole ignition event candidates were selected from a parent sample of spectrally classified non-active galaxies (2.394.312 objects), which currently show optical flux variability indicative of a type I AGN, according to the ALeRCE light curve classifier. A second epoch spectrum for a sample of candidate newborn AGNs was obtained with the SOAR telescope to search for new AGN features. We present the spectral results for the most convincing case of new AGN activity for a galaxy with a prior star-forming optical classification, where the second epoch spectrum shows the appearance of prominent, broad Balmer lines, without any significant changes seen in the narrow line flux ratios. The long-term optical light curves show a steady increase in luminosity starting 1.5 years after the SDSS spectrum was taken and continuing for at least 7 years. Mid-infrared (MIR) colors from the WISE catalog have also evolved from typical non-active galaxy colors to AGN-like colors. Recent X-ray flux detections confirm its nature as an AGN.

Biophysical mechanisms of myocardium sodium channelopathies.

Genetic variants of gene SCN5A encoding the alpha-subunit of cardiac voltage-gated sodium channel Nav1.5 are associated with various diseases, including long QT syndrome (LQT3), Brugada syndrome (BrS1), and progressive cardiac conduction disease (PCCD). In the last decades, the great progress in understanding molecular and biophysical mechanisms of these diseases has been achieved. The LQT3 syndrome is associated with gain-of-function of sodium channels Nav1.5 due to impaired inactivation, enhanced activation, accelerated recovery from inactivation or the late current appearance. In contrast, BrS1 and PCCD are associated with the Nav1.5 loss-of-function, which in electrophysiological experiments can be manifested as reduced current density, enhanced fast or slow inactivation, impaired activation, or decelerated recovery from inactivation. Genetic variants associated with congenital arrhythmias can also disturb interactions of the Nav1.5 channel with different proteins or drugs and cause unexpected reactions to drug administration. Furthermore, mutations can affect post-translational modifications of the channels and their sensitivity to pH and temperature. Here we briefly review the current knowledge on biophysical mechanisms of LQT3, BrS1 and PCCD. We focus on limitations of studies that use heterologous expression systems and induced pluripotent stem cells (iPSC) derived cardiac myocytes and summarize our understanding of genotype-phenotype relations of SCN5A mutations.

Digitalization of Educational Activities at the Municipal Level

The article examines the activity of the municipality from the point of view of the education management system in modern realities, namely in the conditions of digital transformation of society and its life, in particular, digitalization of educational activities. The main advantages and disadvantages of the digitalization of education are analyzed and presented. In the context of the research, the theoretical, normative and legal aspects of the current educational activity are presented, as a key link in solving problems of any nature for the benefit of the local population, in particular at the municipal level. In conclusion, the priority directions of the development of education management in the conditions of digitalization are given, which should effectively influence the optimization of organizational and management processes in the field of digital transformation, as well as the active penetration of digital technologies into the educational process of various educational organizations.
 The article reveals the effectiveness of information and communication technologies in municipal educational institutions training future specialists. In the context of the implementation of the research goal, the role of digitization as a factor in the implementation of educational activities in the process of training specialists in the economic field is studied. In the modern conditions of the development of the information society, there is a need for fast and high-quality calculation of economic indicators. It is this need that prompts the widespread use of software accounting methods. Digitalization has absorbed various fields of human activity.

Addressing ocean planning challenges in a highly crowded sea space: a case study for the regional sea of Catalonia (Western Mediterranean)

Background This study performs an exploratory analysis of current-future sustainability challenges for ocean planning for the regional seas of Catalonia located in the Western Mediterranean (Spain). Methods To address the challenges we develop an Maritime Spatial Planning (MSP)-oriented geodatabase of maritime activities and deploy three spatial models: 1) an analysis of regional contribution to the 30% protection commitment with Biodiversity Strategy 2030; 2) a spatial Maritime Use Conflict (MUC) analysis to address current and future maritime activities interactions and 3) the StressorGenerator QGIS application to locate current and anticipate future sea areas of highest anthropogenic stress. Results & Conclusions Results show that the i) study area is one of the most protected sea areas in the Mediterranean (44–51% of sea space protected); ii) anthropogenic stressors are highest in 1–4 nautical miles coastal areas, where maritime activities agglomerate, in the Gulf of Roses and Gulf of Saint Jordi. iii) According to the available datasets commercial fishery is causing highest conflict score inside protected areas. Potential new aquaculture sites are causing highest conflict in Internal Waters and the high potential areas for energy cause comparably low to negligible spatial conflicts with other uses. We discuss the added value of performing regional MSP exercises and define five challenges for regional ocean sustainability, namely: Marine protection beyond percentage, offshore wind energy: a new space demand, crowded coastal areas, multi-level governance of the regional sea and MSP knowledge gaps.

Disaster Management and Landslide Risk Reduction Strategies in The Gebog Sub-District of Kudus Regency, Central Java, Indonesia

Historically, the Kudus Regency in Central Java Province, Indonesia, has been prone to landslides. This study was conducted in the Gebog Sub-District of Kudus Regency, Central Java, Indonesia. The objectives of this study are: (1) to analyze the level of landslide disaster risk in the Gebog Sub-District, (2) to assess the current community-based landslide risk management activities undertaken by the local population in the Gebog Sub-District and (3) to formulate community-based landslide risk reduction management strategies to mitigate landslide risk. Variables for the level of landslide disaster risk include landslide hazards/threats, vulnerability to landslide hazards and community capacity to deal with landslides. Variables related to the management of landslide risk studied encompass pre-disaster, during-disaster and post-disaster activities by the community. Meanwhile, the variables for community-based landslide risk reduction management strategies include threat reduction, vulnerability reduction and enhancing community capacity before, during and after a landslide disaster. The research design is based on field surveys with 99 individuals as research subjects and 33 field units as samples. Data was collected through questionnaires and interviews and analysis was conducted using scoring and ranking. The research findings indicate that the current community-based landslide risk management activities are still low. From the research and focus group discussions, new strategies for community-based landslide risk reduction management were identified to reduce landslide risk.

A triggered DNA nanomachine with enzyme-free for the rapid detection of telomerase activity in a one-step method

BackgroundTelomerase is considered a biomarker for the early diagnosis and clinical treatment of cancer. The rapid and sensitive detection of telomerase activity is crucial to biological research, clinical diagnosis, and drug development. However, the main obstacles facing the current telomerase activity assay are the cumbersome and time-consuming procedure, the easy degradation of the telomerase RNA template and the need for additional proteases. Therefore, it is necessary to construct a new method for the detection of telomerase activity with easy steps, efficient reaction and strong anti-interference ability. ResultsHerein, an efficient, enzyme-free, economical, sensitive, fluorometric detection method for telomerase activity in one-step, named triggered-DNA (T-DNA) nanomachine, was created based on target-triggered DNAzyme-cleavage activity and catalytic molecular beacon (CMB). Telomerase served as a switch and extended few numbers of (TTAGGG)n repeat sequences to initiate the signal amplification in the T-DNA nanomachine, resulting in a strong fluorescent signal. The reaction was a one-step method with a shortened time of 1 h and a constant temperature of 37 °C, without the addition of any protease. It also sensitively distinguished telomerase activity in various cell lines. The T-DNA nanomachine offered a detection limit of 12 HeLa cells μL−1, 9 SK-Hep-1 cells μL−1 and 3 HuH-7 cells μL−1 with a linear correlation detection range of 0.39 × 102–6.25 × 102 HeLa cells μL−1 for telomerase activity. SignificanceIn conclusion, our study demonstrated that the triggered-DNA nanomachine fulfills the requirements for rapid detection of telomerase activity in one-step under isothermal and enzyme-free conditions with excellent specificity, and its simple and stable structure makes it ideal for complex systems. These findings indicated the application prospect of DNA nanomachines in clinical diagnostics and provided new insights into the field of DNA nanomachine-based bioanalysis.

Sustainable bioelectric activation of periodate for highly efficient micropollutant abatement

The periodate (PI)-based advanced oxidation process is valued for environmental remediation, but current activation methods involve high costs, secondary contamination risks, and limited applicability due to external energy inputs (e.g., UV), catalyst incorporation (e.g., Fe2+), or environmental modifications (e.g., freezing). In this work, novel bioelectric activation of PI using the electrons generated by electroactive bacteria was developed and investigated for rapid removal of carbamazepine (CBZ), achieving 100 %, 100 %, and 76 % removal efficiency for 4.22 µM of CBZ in 20 min at pH 2, 120 min at pH 6.4, and HRT of 30 min at pH 8.5, respectively, with a 1 mM PI dose and without an input voltage. It was deduced that electrons derived from bacteria could directly activate PI using Ti mesh electrodes and generate •IO3 via single electron transfer under strongly acidic conditions (e.g., pH 2). Nevertheless, under weak alkaline conditions (e.g., pH 8.5), biogenic electrons indirectly activated PI by generating OH−via 4e−reduction at the Ti mesh cathode, resulting in the formation of •O2− and 1O2. In addition to the metal cathode, a carbon-based cathode finely modulates the 2e−reduction, yielding H2O2 and activating PI to mainly form •OH. Moreover, primarily non-toxic IO3− was produced during treatment, while no detectable reactive iodine species (HOI, I2, and I3−) were observed. Furthermore, the bioelectric activation of PI demonstrated its capability to remove various micropollutants present in secondary-treated municipal wastewater, showcasing its broad-spectrum degradation ability. This study introduces a novel, cost-effective, and environmentally friendly PI activation technique with promising applicability for micropollutant elimination in water treatment.

Actual trajectory of strategic management development as a science, in the conditions of dynamically developing markets and external challenges

The article considers the current trajectory of strategic management development as a science in the context of dynamically developing markets and external challenges. The use of strategic management tools is crucial in the activities of enterprises, as they provide the basis for identifying, analyzing and responding to external and internal factors and threats. These tools can help companies develop strategies that will allow them to compete effectively in their industry, achieve their goals and stay ahead of their competitors. This article indicates the main areas where strategic management as a science needs to focus its attention, develop research potential, and look for opportunities to implement in the current activities of companies. The methods of analysis of companies’ strategy aimed at identifying, assessing and managing risks that may affect the ability of the organization to achieve its goals, such as SWOT–analysis and ERM, are considered. The methods of forming strategies of economic, industrial and social character to stimulate effective work of the companies’ employees are considered.

Analysis of the educational and cultural activity of the Spanish government in social media: a comparison between pandemic and post-pandemic times

The COVID-19 pandemic challenged education systems as a whole, which had to act on emergency and without previous experience. The aim of this study is to examine the Spanish Government's response to the lockdown scenario through social media and the current (post-pandemic) activity. We collected the Twitter output of the 11 accounts linked to educational and cultural bodies and institutions of the Spanish Government and the interaction of citizens with them. We undertook analyses of social media output in pandemic and post-pandemic times. At the same time, we conducted a content analysis of the 126 tweets posted during the pandemic that had the greatest impact. The results point to increased production during the pandemic and a peak in interactions during the period of strict lockdown. The qualitative analysis reveals that Twitter is mainly used as an information and unidirectional communication board, where the Spanish Government's commitment to resources and tools based on open licences stands out, offering alternatives for Education in times of COVID-19, mainly to teachers. Finally, the analysis has allowed us to identify elements of success in social media communication.

Development and prenatal exposure to androgens alter potassium currents in gonadotropin-releasing hormone neurons from female mice.

Pulsatile gonadotropin-releasing hormone (GnRH) release is critical for reproduction. Disruptions to GnRH secretion patterns may contribute to polycystic ovary syndrome (PCOS). Prenatally androgenized (PNA) female mice recapitulate many neuroendocrine abnormalities observed in PCOS patients. PNA and development induce changes in spontaneous GnRH neuron firing rate, response to synaptic input, and the afterhyperpolarization potential of the action potential. We hypothesized potassium currents are altered by PNA treatment and/or development. Whole-cell patch-clamp recordings were made of transient and residual potassium currents of GnRH neurons in brain slices from 3-week-old and adult control and PNA females. At 3 weeks of age, PNA treatment increased transient current density versus controls. Development and PNA altered voltage-dependent activation and inactivation of the transient current. In controls, transient current activation and inactivation were depolarized at 3 weeks of age versus in adulthood. In GnRH neurons from 3-week-old mice, transient current activation and inactivation were more depolarized in control than PNA mice. Development and PNA treatment interacted to shift the time-dependence of inactivation and recovery from inactivation. Notably, in cells from adult PNA females, recovery was prolonged compared to all other groups. Activation of the residual current occurred at more depolarized membrane potentials in 3-week-old than adult controls. PNA depolarized activation of the residual current in adults. These findings demonstrate the properties of GnRH neuron potassium currents change during typical development, potentially contributing to puberty, and further suggest PNA treatment may both alter some typical developmental changes and induce additional modifications, which together may underlie aspects of the PNA phenotype. There was not any clinical trial involved in this work.

Urinary podocyte markers of disease activity, therapeutic efficacy, and long-term outcomes in acute and chronic kidney diseases.

A critical degree of podocyte depletion causes glomerulosclerosis, and persistent podocyte loss in glomerular diseases drives the progression to end-stage kidney disease. The extent of podocyte injury at a point in time can be histologically assessed by measuring podocyte number, size, and density ("Biopsy podometrics"). However, repeated invasive renal biopsies are associated with increased risk and cost. A noninvasive method for assessing podocyte injury and depletion is required. Albuminuria and proteinuria do not always correlate with disease activity. Podocytes are located on the urinary space side of the glomerular basement membrane, and as they undergo stress or detach, their products can be identified in urine. This raises the possibility that urinary podocyte products can serve as clinically useful markers for monitoring glomerular disease activity and progression ("Urinary podometrics"). We previously reported that urinary sediment podocyte mRNA reflects disease activity in both animal models and human glomerular diseases. This includes diabetes and hypertension which together account for 60% of new-onset dialysis induction patients. Improving approaches to preventing progression is an urgent priority for the renal community. Sufficient evidence now exists to indicate that monitoring urinary podocyte markers could serve as a useful adjunctive strategy for determining the level of current disease activity and response to therapy in progressive glomerular diseases.

Discovery of diffuse radio source in Abell 1060

Abstract Non-thermal components in the intra-cluster medium (ICM), such as turbulence, magnetic field, and cosmic rays, imprint the past and current energetic activities of jets from active galactic nuclei (AGN) of member galaxies as well as disturbance caused by galaxy cluster mergers. Meter- and centimeter-radio observations of synchrotron radiation allow us to diagnose the nonthermal component. Here we report on our discovery of an unidentified diffuse radio source, named the Flying Fox, near the center of the Abell 1060 field. The Flying Fox has an elongated ring-like structure and a central bar shape, but there is no obvious host galaxy. The average spectral index of the Flying Fox is −1.4, which is steeper than that for radio sources seen at meter wavelengths. We discussed the possibilities of radio lobes, phoenixes, radio halos and relics, and an odd radio circle. In conclusion, the Flying Fox is not clearly explained by known radio sources.

Allosteric Activation of α7 Nicotinic Acetylcholine Receptors by Novel 2-Arylamino-thiazole-5-carboxylic Acid Amide Derivatives for the Improvement of Cognitive Deficits in Mice.

Enhancing α7 nAChR function serves as a therapeutic strategy for cognitive disorders. Here, we report the synthesis and evaluation of 2-arylamino-thiazole-5-carboxylic acid amide derivatives 6-9 that as positive allosteric modulators (PAMs) activate human α7 nAChR current expressed in Xenopus ooctyes. Among the 4-amino derivatives, a representative atypical type I PAM 6p exhibits potent activation of α7 current with an EC50 of 1.3 μM and the maximum activation effect on the current over 48-fold in the presence of acetylcholine (100 μM). The structure-activity relationship (SAR) analysis reveals that the 4-amino group is crucial for the allosteric activation of α7 currents by compound 6p as the substitution of 4-methyl group results in its conversion to compound 7b (EC50 = 2.1 μM; max effect: 58-fold) characterized as a typical type I PAM. Furthermore, both 6p and 7b are able to rescue auditory gating deficits in mouse schizophrenia-like model of acoustic startle prepulse inhibition.